Early detection of cancer is deemed to be a key to successful and cost effective cancer treatment. Routine monitoring of plasma biomarker levels is a non-invasive method for screening for cancer and monitoring for recurrence after treatment. In order to detect the presence of relevant biomarker levels in plasma, high affinity, highly specific capture reagents must be developed targeting tryptic peptides. During the phase I contract proof-of concept phase, utilizing our proprietary Smart FusionTM and SeleKDt Technology, we have successfully delivered high affinity anti-peptide mouse monoclonal antibodies (mAbs) against 10 peptides representing 6 biomarkers with a high success rate. We showed that these antibodies perform well in mass spectrometry-based cancer biomarker quantitation methods such as SISCAPA-MRM to enable precise measurement of protein biomarkers in patient plasma. In this Phase II application, we propose to fully implement these approaches to develop ~100 high affinity mAbs against biomarker peptides representing 50 known and putative cancer protein biomarkers as a basis for SISCAPA immuno-MRM assays useful in biomarker validation, clinical research and, ultimately, in clinical assays.